The deleterious effects of sofosbuvir and ribavirin (antiviral drugs against hepatitis C virus) on different body systems in male albino rats regarding reproductive, hematological, biochemical, hepatic, and renal profiles and histopathological changes.

Sofosbuvir is one of the crucial drugs used in the treatment of chronic hepatitis C virus (HCV) in adults and children with compensated liver disease, including cirrhosis. It may be used alone or with other drugs. Ribavirin is an antiviral medication used to treat HCV infection. It is not effective when used alone and must be used in combination with other medications, such as sofosbuvir. This study pertains to a comprehensive assessment of the deleterious effects of sofosbuvir (an antiviral drug against chronic HCV) or sofosbuvir combined with ribavirin (an antiviral drug against RNA and DNA viruses) on several biological activities of the body, including hematological, hormonal, biochemical, histological, and immunohistochemical examinations during a long-standing period on male healthy rats. In addition, fertility assessments were performed, including sperm collections and semen parameter investigations. This study was conducted on 21 male rats divided into three equal groups. Group I (control group) received distilled water; group II (sofosbuvir group) received sofosbuvir (4 mg/kg); and group III (sofosbuvir + ribavirin) received sofosbuvir (4 mg/kg) plus ribavirin (30 ml/kg). All groups received the specific drug for six months. Blood and tissue samples were collected for hematological, hormonal, biochemical, histological, and immunohistochemical examinations. In addition, sperm collection and assessments of semen parameters were performed. Results revealed that sofosbuvir causes a highly significant decrease in the mean of most hematological, immunological, hormonal, and biochemical parameters, except for a few numbers of parameters such as neutrophils, monocytes, basophils, cortisol, GOT, and lipase, which exhibit a significant increase. The same occurred in the sofosbuvir + ribavirin group, but at much higher levels, as most hematological, immunological, hormonal, and biochemical parameters exhibit a highly significant decrease except for monocytes, triglyceride, and lipase, which exhibit a significant increase. When compared to the sofosbuvir group alone, the sofosbuvir + ribavirin group demonstrated a highly significant decline in the mean of most hematological, immunological, hormonal, and biochemical parameters except lymphocytes and triglycerides, which exhibit a substantial increase. For the reproductive parameters, both groups exhibit a significant decrease in the total sperm motility percentage. Finally, it can be concluded that sofosbuvir causes acute pancreatitis and combined immunodeficiency. Ribavirin is associated with hormonal deficiency, which indicates the occurrence of hypopituitarism. Moreover, sofosbuvir and ribavirin synergistically affect myelosuppression and cause iron-deficiency anemia. However, sofosbuvir, or its combination with ribavirin, is associated with a reduced risk of hepatocellular carcinoma. Besides, adding ribavirin to be combined with sofosbuvir improved the immunodeficiency caused by sofosbuvir; this confirms that using ribavirin with sofosbuvir reduces the side effects of both alone.

Treatment of Inactive Ovaries of Holstein Dairy Cows by Epidural Injection of GnRH Analogue (Receptal) and Its Impact on the Reproductive Hormones, Oxidant/Antioxidant Profile and Micro and Macro-Elements Profile.

This study was designed to evaluate a new therapeutic approach for inactive ovaries based on the epidural administration of a GnRH agonist (Receptal) and an investigation of the impact of this treatment on the hormonal, oxidant/antioxidant and micro- and macro-element profiles. Sixty cows with postpartum anestrus were divided into two groups: the first group (group Repid, n = 30) was administered an epidural injection of Receptal, while the second group (group Cepid, n = 30) received saline and was considered the control group. Evaluation of hormonal (progesterone, FSH, LH, testosterone, and cortisol), oxidant/antioxidant (MDA, SOD, GPx and TAC) as well as micro- and macroelement (calcium, phosphorus, manganese and magnesium) profiles was done in serum. The results showed that the epidural injection of Receptal has the potential to induce estrus response and conception incidence in treated cows. Compared to the control group, progesterone, FSH, and LH concentrations were significantly increased in the treated group, whereas testosterone and cortisol decreased (p < 0.05) following treatment. In addition, the treated group had greater TAC and GPx concentrations than the control group. Serum concentrations of magnesium increased (p < 0.05) following receptal treatment, but differences in other minerals were not detected. This research suggests a novel, effective method of treating inactive ovaries with epidural infusion of a GnRH agonist.

Abortion associated with postpartum opportunistic bacterial invasion reduces fertility and induces disturbances of reproductive hormones, hematological profile, and oxidant/antioxidant profiles in dairy cows.

Objective: The following study examines for the first time the changes that occur in the post-partum period following abortion in the first trimester of dairy cows using hormonal, hematological, and oxidant/antioxidant profiles. In addition, a bacteriological examination was also performed to explore the role of infections in the complications that occur during this period. Materials and Methods: One hundred cows were split into two equal groups: The first group enrolled cows that suffered from abortion in the first trimester. The second group enrolled cows that did not experience abortion problems (the control group). Uterine swabs were collected from cows. Blood samples were collected for hormonal, hematological, and oxidative profiles. Results: Results reveal that Escherichia coli, Staphylococcus spp., and Streptococcus spp. are the opportunistic bacteria that were isolated from abortive cows with multidrug-resistant (MDR) characteristics. Red blood cell (RBC) count, hemoglobin, mean corpuscular hemoglobin (MCH), and MCH concentration (MCHC) were significantly higher in the abortive group than in controls in the first 3 days after calving. Conversely, total leukocyte count, platelet count, neutrophils, eosinophils, and immunoglobulin G and M were significantly lower in the abortion group than in controls. The concentrations of estradiol, prostaglandin F2α, oxytocin, and cortisol are significantly increased in the abortive cows, while progesterone is significantly decreased. The levels of malondialdehyde (MDA) were higher in the abortive group, while the levels of superoxide dismutase (SOD), glutathione peroxidase (GPx), and total antioxidant capacity (TAC) were lower. Conclusion: Abortion during the first trimester of pregnancy increases the risk of postpartum opportunistic bacterial invasion of the uterus. Oxidative stress (OS) and neutropenia are the most important findings that may occur in the postpartum period after abortion and may be due to the abortion itself or its predisposition to opportunistic bacterial invasion of the uterus, which finally causes a fertility reduction.

Ameliorative Effect of Oxytocin on FBN1 and PEPCK Gene Expression, and Behavioral Patterns in Rats' Obesity-Induced Diabetes.

Amelioration of hyperinsulinemia and insulin resistance associated with obesity is a cardinal target for therapeutics. Therefore, we investigated the relation of Fibrilln-1 (FBN1) mRNA expression and hepatic phosphoenolpyruvate caboxykinase (PEPCK) enzyme to the ameliorative impact of oxytocin on obesity-induced diabetes, suggesting glycogenolysis markers in diabetic models. Four groups of forty male Wistar rats were formed (n = 10): a control group fed basal diet and intraperitoneal injections of saline; an oxytocin-injected group; a diet-induced obese group fed a high-fat/high-sugar diet and injected with saline; a diet-induced obese group injected with oxytocin. Depending on blood glucose levels, obese groups were further sub-grouped into prediabetic, and diabetic rats, with 5 rats each, at the ninth and the 16th week of the feeding period, respectively. FBN1 expression and PEPCK activity were determined using the qPCR technique and some biochemical parameters (glycemic, lipid profile, kidney, and liver functions) were determined using kits. Obese groups showed an elevation of brain FBN1 expression, high serum lipid profile, high glucose level, and a deleterious impact on liver and kidney functions. Obese groups showed the stimulator effect of the PEPCK enzyme and time-dependent pathological changes in renal and hepatic tissues. The motor activities were negatively correlated with FBN1 gene expression in prediabetic and diabetic rats. In addition to our previous review of the crucial role of asprosin, here we showed that oxytocin could ameliorate obesity-induced diabetes and decrease FBN1 gene expression centrally to block appetite. Oxytocin caused decreases in PEPCK enzyme activity as well as glycogenolysis in the liver. Therefore, oxytocin has a potential effect on FBN1 expression and PEPCK enzyme activity in the obesity-induced diabetic-rat model.

Protective effects of Folic acid against reproductive, hematological, hepatic, and renal toxicity induced by Acetamiprid in male Albino rats.

Acetamiprid (ACP) is a widespread used insecticide belonging to neonicotinoids (NNs) that are introduced for controlling pests, and for domestic use to control fleas on cats and dogs. The current experiment pertains to a comprehensive overview of the toxic effects of acetamiprid and the protective role of folic acid against reproductive, hematological, histopathological and biochemical toxicity induced by ACP during 5 weeks. Male Albino rats were divided into four groups of seven each: First group served as control rats (CL group); Second group received acetamiprid (ACP group) (10 mg/Kg body weight) by oral gavage. Third group received both acetamiprid and folic acid (ACP + FA group) (2 mg/Kg body weight); Fourth group received folic acid (FA group) (2 mg/Kg body weight). Exposure of rats to acetamiprid caused significant changes in the reproductive indices as it cause a significant decrease in the sperm count, viability and motility. Furthermore, reproductive hormones such as testosterone and gonadotropin-releasing hormones (GnRH) were found significantly decreased in acetamiprid treated group. In addition, acetamiprid administration causes significant changes of some hematological and immunological parameters (red blood cells (RBC), hemoglobin (Hb), platelet (Plt), white blood cells (WBCs), lymphocyte, monocyte, neutrophil, eosinophil, IgG, IgM and IgA) in treated rats compared to controls. Significant increases in the levels of hepatic markers enzymes (aspartate transaminase (AST), Alanine transaminase (ALT), alkaline phosphatase (ALP) in acetamiprid treated group, as well as severe toxic effect was found on the liver and kidney after acetamiprid delivery according to the histopathological examinations which were confirmed after applying histological, histochemical, and Immunohistochemistry tests. The most conspicuous histopathological changes occurred on the liver and kidney of the acetamiprid treated group represented in the liver by fatty liver cells, leukocytic infiltration, and hemorrhage while in kidney tissues revealed tubular atrophy, dense eosinophilic cytoplasm and dilated congested blood vessels. Both liver and kidney tissues showed an increase in the amount of collagenous fibers and immune reactivity of fatty acid synthase. Moreover, other markers such as uric acid and total antioxidant capacity (TAC) were significantly decreased in acetamiprid treated rats. Co-administration of folic acid to the third group restored all the parameters cited above to near-normal values. Therefore, our investigation revealed that acetamiprid induce severe toxicity on different body systems and parameters and folic acid appeared to be a promising agent for protection against acetamiprid-induced toxicity.

Pomegranate Peel Extract Is a Potential Alternative Therapeutic for Giardiasis.

Giardiasis is a major diarrheal disease affecting approximately 2.5 million children annually in developing countries. Several studies have reported the resistance of Giardia lamblia (G. lamblia) to multiple drugs. Therefore, identifying an effective drug for giardiasis is a necessity. This study examined the antiparasitic effect of Punica granatum (pomegranate) and evaluated its therapeutic efficacy in rats infected with G. lamblia. In vitro study showed high efficacy of pomegranate peel ethanolic extract in killing G. lamblia cysts as demonstrated by eosin vital staining. We showed that treating infected rats with pomegranate extract resulted in a marked reduction in the mean number of G. lamblia cysts and trophozoites in feces and intestine respectively. Interestingly, the number of G. lamblia trophozoites and cysts were significantly lower in the pomegranate extract-treated group compared to the metronidazole-positive control group. Moreover, pomegranate extract treatment significantly induced nitric oxide (NO) and reduced serum IL-6 and TNF-α, compared to infected untreated rats. Histological and scanning electron microscopy (SEM) examination of the jejunum and duodenum of pomegranate extract-treated animals confirmed the antiparasitic effect of the extract, and demonstrated the restoration of villi structure with reduction of villi atrophy, decreased infiltration of lymphocytes, and protection of intestinal cells from apoptotic cell death. In conclusion, our data show that the pomegranate peel extract is effective in controlling G. lamblia infections, which suggests that it could be a viable treatment option for giardiasis.

A Complementary Herbal Product for Controlling Giardiasis.

Giardiasis is an intestinal protozoal disease caused by Giardia lamblia. The disease became a global health issue due to development of resistance to commonly used drugs. Since many plant-derived products have been used to treat many parasitic infestations, we aimed to assess the therapeutic utility of Artemisia annua (A. annua) for giardiasis. We showed that NO production was significantly reduced whereas serum levels of IL-6, IFN-γ, and TNF-α were elevated in infected hamsters compared to uninfected ones. Additionally, infection resulted in increased numbers of intraepithelial lymphocytes and reduced villi heights, goblet cell numbers, and muscularis externa thickness. We also showed that inducible NO synthase (iNOS) and caspase-3 were elevated in the intestine of infected animals. However, treatment with A. annua significantly reduced the intestinal trophozoite counts and IEL numbers, serum IL-6, IFN-γ, and TNF-α, while increasing NO and restoring villi heights, GC numbers, and ME thickness. Moreover, A. annua treatment resulted in lower levels of caspase-3, which indicates a protective effect from apoptotic cell death. Interestingly, A. annua therapeutic effects are comparable to metronidazole. In conclusion, our results show that A. annua extract is effective in alleviating infection-induced intestinal inflammation and pathological effects, which implies its potential therapeutic utility in controlling giardiasis.

The deleterious effect of postpartum pyometra on the reproductive indices, the metabolic profile, and oxidant/antioxidant parameters of dairy cows.

BACKGROUND AND AIM: Postpartum uterine infectious diseases, such as pyometra, have discrepancy with both health and, subsequently, productivity of dairy cows due to its high prevalence and the high cost of treatment. Therefore, this study investigates the influence of pyometra on the reproductive indices, the metabolic profile, and oxidant/antioxidant parameters of the pyometric animal compared to those of healthy ones. MATERIALS AND METHODS: The study included 30 cows. The animals were differentiated into two groups of 15 cows each: A group of pyometra and a control group. All pyometric cows were subjected to breeding soundness examination after the end of pyometra and were compared to the control group. Blood samples were obtained to assess the levels of glucose, non-esterified fatty acids (NEFA), triglycerides (TGs), cholesterol, albumin, total protein, alanine aminotransferase, aspartate aminotransferase (AST), alkaline phosphatase (ALP), blood urea nitrogen (BUN), creatinine, calcium (Ca), phosphorus, sodium, potassium, progesterone hormone (P4), malondialdehyde (MDA), total antioxidant capacity (TAC), glutathione peroxidase (GPx), and superoxide dismutase. RESULTS: Results revealed significant prolonged duration of first estrus, the days open, and the required number of services due to pyometra. The pyometra group yielded increased levels of NEFA, TGs, ALP, BUN, creatinine, MDA, and progesterone hormone. In addition, significant decrease in the levels of glucose, cholesterol, albumin, Ca, phosphorus, sodium, TAC, GPx, and superoxide dismutase was observed in the pyometra group. Finally, no difference in the concentrations of total protein, ALT, AST, and potassium was observed in the pyometra group. CONCLUSION: The reproductive indices was adversely influenced in cows with postpartum pyometra, and metabolic profile, involving energy balance signals and liver function indicators, revealed differences between the two groups. Increased levels of oxidative stress parameters and decrease levels of antioxidant levels were also found, suggesting that pyometra is an incentive for oxidative stress. Overall, checking the energy balance, metabolic imbalances, and oxidant/antioxidant profile, accompanied with pre-emptive procedures during the postpartum period, is essential and can reduce the chances of such diseases and possible noxious results in highly productive cows.

Changes of reproductive indices of the testis due to Trypanosoma evansi infection in dromedary bulls (Camelus dromedarius): Semen picture, hormonal profile, histopathology, oxidative parameters, and hematobiochemical profile.

OBJECTIVE: IThis study was designed for the investigation of the effect of infection by Trypanosoma evansi on the changes of reproductive indices of the testis, causing reproductive failure in dromedary bulls (Camelus dromedarius). MATERIALS AND METHODS: Seventy-five bulls were used for monitoring of the changes in the semen characteristics, reproductive hormones, hematobiochemical profiles, histopathological characters in the testis, and oxidative biomarkers. The animals were divided into two groups. Group A represented the uninfected or control group, while group B represented the infected group. Group B was again divided into two subgroups, such as acute and chronic infected animals. RESULTS: Results showed that the semen analysis of infected camels revealed the presence of alterations in the morphology of sperms, especially the heads and tails, as compared to control animals. The hormonal profile indicated a significant decrease in the luteinizing hormone, follicle- stimulating hormone, and testosterone levels, accompanied by the rise in the cortisol level in infected camels compared with the negative control. The histopathology and testicular degeneration were found to be associated with other disorders in infected camels. The oxidative profile and protein oxidation were promoted in infected testicles, indicating the occurrence of harmful effects in the cell. CONCLUSION: It is concluded that T. evansi infection in dromedary bulls causes severe damage to the testicular tissue and decreases the reproductive hormone levels associated with severe morphological disorders in sperms due to oxidative stress resulting from the infection. All these findings indicate that T. evansi can cause reproductive failure and fertility damage.

Synchronization with controlled internal drug release (CIDR) and prostaglandin F2α (PGF2α) influences oxidant/antioxidant biomarkers and mineral profile in summer-stressed anoestrous buffalo (Bubalus bubalis).

During the summer season, high ambient temperature in tropical and subtropical countries exposes buffaloes to oxidative stress that have antigonadotropic and antisteroidogenic effects. Uses of hormonal therapy can improve the state of ovarian inactivity caused by heat stress and cause anoestrous buffaloes to come into oestrus and successfully achieve pregnancy. Therefore, this study was designed to detect the role of oxidative stress in production of the anoestrous state in summer heat stressed buffaloes and the effects of treatment by Controlled internal drug release (CIDR) in solving of this problem. Also it monitored the changes in Oxidant/antioxidant biomarkers and mineral profile before and after the treatment. Forty buffaloes with no signs of oestrus for more than 120 days after calving were selected. The animals were divided into two groups: the first group (group I, n = 25) was subjected to treatment with CIDR, while the second group (group II) received no treatment and was considered the control group (n = 25). Blood samples were collected before treatment, after treatment and after 45 days of oestrus. The serum level of TAC, MDA, NO, ascorbic acid (vitamin C), P, Cu and Zn were measured. The results showed that 80% of treated buffaloes came into oestrus. The conception rate was 75%. TAC concentrations were significantly higher in group I than in group II. There were significant decreases in the mean values of MDA, NO and ascorbic acid in the buffaloes in oestrus, but these values increased when the buffaloes became pregnant. In contrast there were no significant differences in the mean values of MDA, NO or ascorbic acid in the buffaloes that came into oestrus but failed to conceive. The mean serum P, Cu and Zn values were significantly increased (P < 0.05) in the buffaloes that came into oestrus compared to the control animals. The levels of P and Zn significantly increased when the buffaloes became pregnant and remained unchanged when they failed to conceive. In conclusion, known physiological and pathological variations in the oxidant/antioxidant parameters and mineral profile of summer anoestrous buffaloes may help to understand this problem of infertility.

Eugenol, a potential schistosomicidal agent with anti-inflammatory and antifibrotic effects against Schistosoma mansoni, induced liver pathology.

INTRODUCTION: Schistosomiasis is one of the most prevalent parasitic infections in developing countries. Although chemotherapy is one of the main strategies in controlling the disease, it is less effective in reversal of schistosome-induced pathology especially in the chronic and advanced stages of schistosomiasis. New strategies and prospective therapeutic agents with antifibrotic effects are needed. Eugenol has a wide anti-inflammatory effect. In the present study, we investigated the possible antischistosomal effect of eugenol on Schistosoma mansoni. MATERIALS AND METHODS: The murine model of S. mansoni was established in three groups of adult male Balb-c mice; group I (infected non-treated group) and groups II and III (infected groups) treated orally with eugenol and praziquantel (PZQ), respectively. The expression of the sensitive immunohistochemical marker α-smooth muscle actin (α-SMA) in schistosome-infected tissues was determined. In addition, parasitological, biochemical, and histological parameters that reflect disease severity and morbidity were examined. RESULTS: Eugenol treatment showed significant reduction in total worm burden by 19.2%; however, the oogram pattern showed no marked difference compared to that of the PZQ group. Yet, eugenol significantly reduced the serum levels of hepatic enzymes: aspartate aminotransferase and alanine aminotransferase. Histopathological examination revealed a significant reduction in both numbers and diameters of hepatic granulomata, which was consistent with reduction in collagen fiber deposition. Additionally, the antifibrotic effect of eugenol was validated by its considerable reduction in the expression of the sensitive marker α-SMA in both eugenol- and PZQ-treated groups. CONCLUSION: Although eugenol could not totally eradicate adults of S. mansoni, the significant amelioration of liver enzymes and hepatic fibrosis potentiate eugenol's role as a promising antifibrotic and a complementary antischistosomal agent.